Substance abuse is a major public health problem among adolescents in the United States, associated with serious negative outcomes including high-risk sexual behavior and the leading causes of adolescent death: accidents, homicide and suicide. Substance use disorders (SUD's) are one of the three most common forms of adolescent psychiatric disturbance. Prevention of such disorders is a public health priority. The National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH) recently released RFA: DA-03-007, calling for investigations into the impact of child psychopathology and childhood interventions on subsequent drug abuse. This project, Substance use Outcomes Following Treatment for Adolescent Depression (SOFTAD) is an extended follow-up of adolescents who have completed the NIMH Treatment for Adolescents with Depression Study (TADS). We developed and are coordinating TADS, a 12-site study comparing cognitive behavior therapy (CBT), fluoxetine (FLX), combined CBT and FLX acutely to one another and to placebo, and longitudinally to one another in 432 adolescents with Major Depressive Disorder (MDD). TADS is the first adolescent MDD treatment study to include measures of substance use and abuse. We propose to enhance the measurement of substance use outcomes and related family factors and to extend the follow-up period from TADS treatment to five years in order to address critical questions emphasized in RFA: DA-03-007. These include the impact of treating MDD (and of specific treatments) on subsequent substance use outcomes, the identification of moderators and mediators of successful outcome in the affective and substance use domains, and the longitudinal relationship between adolescent MDD and substance use or abuse in a clinical sample. Approximately 300 adolescents will be followed and assessed every six months. Self-report, parent-report and diagnostic interview measures will be collected. The major hypothesis, that successful treatment of MDD will reduce subsequent substance use problems, and additional questions, will be tested using chi-square, logistic regression, and structural equation modeling. SOFTAD will be coordinated by the Duke Clinical Research Institute (DCRI), the same organization coordinating TADS, thus realizing substantial efficiencies and cost savings. [unreadable] [unreadable]